Azelex

CLINICAL PHARMACOLOGY

The exact mechanism of action of azelaic acid is not known. The following in
vitro data are available, but their clinical significance is unknown. Azelaic
acid has been shown to possess antimicrobial activity against Propionibacterium
acnes and Staphylococcus epidermidis. The antimicrobial action may be attributable
to inhibition of microbial cellular protein synthesis.

A normalization of keratinization leading to an anticomedonal effect of azelaic acid may also contribute to its clinical activity. Electron microscopic and immunohistochemical evaluation of skin biopsies from human subjects treated with AZELEX (azelaic acid cream) Cream demonstrated a reduction in the thickness of the stratum corneum, a reduction in number and size of keratohyalin granules, and a reduction in the amount and distribution of filaggrin (a protein component of keratohyalin) in epidermal layers. This is suggestive of the ability to decrease microcomedo formation.

Pharmacokinetics

Following a single application of AZELEX (azelaic acid cream) Cream to human skin in vitro,
azelaic acid penetrates into the stratum corneum (approximately 3 to 5% of the applied dose) and other viable skin layers (up to 10% of the dose is found in the epidermis and dermis). Negligible cutaneous metabolism occurs after topical
application. Approximately 4% of the topically applied azelaic acid is systemically
absorbed. Azelaic acid is mainly excreted unchanged in the urine but undergoes
some β-oxidation to shorter chain dicarboxylic acids. The observed half-lives
in healthy subjects are approximately 45 minutes after oral dosing and 12 hours
after topical dosing, indicating percutaneous absorption rate-limited kinetics.

Azelaic acid is a dietary constituent (whole grain cereals and animal products),
and can be formed endogenously from longer-chain dicarboxylic acids, metabolism
of oleic acid, and ψ-oxidation of monocarboxylic acids. Endogenous plasma
concentration (20 to 80 ng/mL) and daily urinary excretion (4 to 28 mg) of azelaic
acid are highly dependent on dietary intake. After topical treatment with AZELEX (azelaic acid cream)
Cream in humans, plasma concentration and urinary excretion of azelaic acid
are not significantly different from baseline levels.

Last reviewed on RxList: 11/11/2008
This monograph has been modified to include the generic and brand name in many instances.